June 2011 Ask the Expert: Clinical Trials

During the month of June, Living Beyond Breast Cancer expert George W. Sledge, Jr., MD, answered your questions about how to access breast cancer clinical trials and research studies, which members of your healthcare team can help you find clinical trials, when to ask about them and the benefits and risks of taking part.

Question: How can I find out about all the drugs in clinical trials for my type of breast cancer?

Dr. Sledge: An excellent source for clinical trials is the National Institute of Health’s ClinicalTrials.gov website, which lists over 100,000 trials with locations in 174 countries. The site is searchable by region and by cancer type. For instance, one can type in “Indianapolis” and “HER2” and get a list of all HER2-targeting trials open in Indianapolis. Closer to home, most NCI-designated cancer centers have their own trials, and frequently those trials cover the waterfront for breast cancer.

Question: Are there any international clinical trials of new medicines for women with HER2 positive metastatic breast cancer for whom trastuzumab (Herceptin) may eventually become ineffective?

Dr. Sledge: There are numerous trials of new agents in HER2-positive metastatic breast cancer. The ClinicalTrials.gov website usually has the most up-to-date listing of these.

There is a long list of interesting agents in development, including pertuzumab (Omnitarg), TDM-1, neratinib and numerous PI3K inhibitors.

In addition, of course, there is already an FDA-approved agent for HER2 positive disease following trastuzumab. This agent is lapatinib (Tykerb), a daily oral medication that interferes with the portion of the HER2 molecule that is inside the breast cancer cell.

Q: Do you know of any vaccine trials a woman with metastatic breast cancer would qualify for?

Dr. Sledge: A search of ClinicalTrials.gov reveals a fairly large number of vaccine-based trials for metastatic breast cancer.

I have not, as a rule, been a big fan of vaccine-based trials for metastatic breast cancer, because it has been difficult to demonstrate that they effectively mobilize the body’s immune system against large volumes of cancer cells. However, there is now renewed interest in immune-based approaches given the recent success of ipilimumab (Yervoy, an antibody therapy that mobilizes T cells to fight melanoma). Many of these new therapies are not vaccine therapies but rather agents that stimulate the immune system in other ways.

Question: I am six years since my diagnosis with stage I breast cancer and post lumpectomy, chemotherapy and radiation, as well as hormonal therapy. Are there trials regarding continued use of hormonal therapy?

Dr. Sledge: There are several past and present trials that have looked at duration of hormonal therapy.

The MA-17 trial looked at postmenopausal women who had received five years of adjuvant tamoxifen and asked whether adding five years of aromatase inhibitor therapy was beneficial. The answer was yes, that five additional years of aromatase inhibitor therapy improved disease-free survival and appeared to improve overall survival in lymph node-positive women.

Beyond this trial, we have several unanswered questions. The very large ATLAS trial (Adjuvant Tamoxifen, Long Against Short) is comparing five years of tamoxifen to 10 years. This trial is still in follow-up, and final results have not yet been presented in public.

Similarly, in postmenopausal women, the MA-17R trial (an extension of MA-17) is comparing five years of aromatase inhibitor therapy to 10 years. While all the women needed to answer this important question have been recruited, we do not yet have the answer. For the moment, neither 10 years of tamoxifen nor 10 years of aromatase inhibition are proven to add benefit, though with the passage of time either might be proven beneficial.

Question: I have triple-negative metastatic breast cancer to the lungs, lymph nodes and abdomen. I just completed paclitaxel (Abraxane)/bevacizumab (Avastin), and my original chemo was doxorubicin (Adriamycin), cyclophosphamide (Cytoxan) and docetaxel (Taxotere). My tumors are stable, but my oncologist thinks I will need more chemo soon, depending on my scans. What is your recommendation for a second metastatic treatment, a clinical trial or an already proven drug? My doctor is suggesting MK2206 and paclitaxel (Taxol), because she says the taxane drugs seem to work best.

Dr. Sledge: There are multiple treatment options available for women with metastatic triple-negative breast cancer who have had prior treatment with Adriamycin and taxanes such as Taxotere and Abraxane. These include standard FDA-approved chemotherapy agents such as gemcitabine (Gemzar), vinorelbine(Navelbine), capecitabine (Xeloda) and eribulin (Halaven), as well as a growing number of investigational agents. In terms of standard chemotherapy agents, I generally prescribe these sequentially rather than in combination, which I think minimizes side effects.

I always encourage patients to enter a clinical trial, if one is available, for this disease, because I am not satisfied with existing chemotherapy options and because I see new drugs as the way forward for triple-negative breast cancer. Most investigational agents come with specific restrictions (called entry or exclusion criteria) for trial participation, and by far the most common reason for exclusion is the number of prior chemotherapy regimens.

So if a woman is interested in trying something new (which I consider quite reasonable here), she should be aggressive in asking her physician what trials are available, both locally and elsewhere. The FDA-approved drugs will always be available later, but a woman can miss the window of opportunity for an exciting new agent.

Question: I am a 10-year metastatic breast cancer patient who is five-and-a-half years out from whole-brain radiation with no recurrences of brain tumors. Do you know of clinical trials seeking long-term survivors like me?

Dr. Sledge: While there are several open trials for patients with recently-diagnosed brain metastasis, I am not aware of any that are open for long-term survivors of brain metastasis. Congratulations on doing so well.

Question: I was diagnosed in April 2010 with stage III IBC (inflammatory breast cancer) and am triple-negative. I did ACT (Adriamycin and Cytoxan treatment) last summer and then a double mastectomy and radiation. I was told all was clear in October, and then it was back in December. I did a trial with gemcitibine (Gemzar) and iniparib in February and March. My CT showed it spread to my liver. I did a round of capecitabine (Xelota) and taxane. Are there other trial drugs to try?

Dr. Sledge: There are definitely other chemotherapy drugs available for metastatic triple-negative breast cancer. These would certainly include eribulin (Halaven), which was just approved last year by the FDA, and vinorelbine (Navelbine). I would also encourage you to look into clinical trials that might be applicable to you through the government’s clinicaltrials.gov website.

Question: My friend, who has triple-negative breast cancer, is BRCA negative and had a recurrence, is now terminal with mets to the breast bone, lymph nodes and lungs. She is fighting for quality for life and won't be seeking chemo this time around because of the fatigue and weakness associated with [that]. Is there any kind of clinical trial you can suggest that would buy her more time that won't make her tired and weak quickly? I really care for my friend and would like to think there is something she can take to slow the progression of her cancer.

Dr. Sledge: The answer to this question depends a great deal on what prior therapies your friend has had. Most chemotherapy agents (the principal available therapies for TNBC) promote fatigue to varying degrees, though if the fatigue and weakness are related to the cancer itself (for instance, anemia related to bone marrow involvement), then in some cases a response to therapy will decrease fatigue and improve quality of life.

It is also important to point out that how long a woman receives therapy for advanced breast cancer should always be the woman’s decision based upon open and forthright discussions with her oncologist as to her likelihood of benefit and harm with available agents.

Question: I heard there's a new drug for triple-negative breast cancer on the horizon that's better than sunitinib (Sutent) and lapatinib (Tykerb). Do you know what this new drug is? Is this a new clinical trial for triple-negative breast cancer?

Dr. Sledge: There are large numbers of novel agents being tested for TNBC, though no particular agent is so far along that I would consider it a “slam-dunk” to come on the market in the near future. What many of us thought of as the best bet for rapid approval, the PARP inhibitor that looked so good in Phase II trials in 2009, has recently failed to meet its primary endpoints in a recently reported Phase III trial.